Screening for compounds that may provide a therapeutic benefit can involve assays based upon the relationship between cell surface receptors and their natural binding partners, or ligands. In general, such assays are often developed which measure some biological signal caused by the binding of the ligand to the receptor. Compounds are then screened to determine those that can bind to the receptor, by blocking the binding of the ligand thereto, and determining what type of signal is caused by the compound—for example, the signal can be enhanced (sometimes referred to as an “agonist”) or the signal can be decreased (sometimes referred to as an “antagonist). Compounds evidencing the desired binding and biological signal are then often tested in animals to determine if these compounds may provide a therapeutic benefit to humans (and in some cases, animals for animal therapeutics).
One condition for which only a limited number of medicinal remedies are currently available is emesis. Emesis (vomiting) is a common symptom of a variety of disorders, brought on by events including the administration of chemotherapeutic agents, motion, pregnancy (morning sickness), and infections. As unpleasant as emesis and the related sensation of nausea may be, they are important in many cases for survival. Emesis is often triggered by the introduction of poisons into the body, such that the body must rapidly eject such poison from the body. Not all species are capable of an emetic response. For example, rats are incapable of having emesis induced by agents that they ingest, which is the main reason why rats that eat poison cannot remove the poison from their bodies, and thus die. In humans, anti-emetic therapy generally involves removing the offending stimulus or resolving the condition responsible for the emesis.
Current therapeutic agents for emesis often have undesired side effects, such as sedation or anxiety. As such, there is a need for improved anti-emetic compounds are necessary (see, e.g., Horn, Charles, C. “Is there a need to identify new anti-emetic drugs?” Drug Discov Today Ther Strateg. 2007; 4(3):183-187).